Substituted halogen-phenols



Patented "Dec. '12, 1933 UNITED STATES 1,938,911 SUBSTITUTEDn'ALoGEN-PnENoLs Emil Klarmann, Jersey City, and Louis W. Gates,Bloomfield, N. 1., assignors to Lehn & Fink, Inc., Bloomfield, N. 1., acorporation of Delaware No Drawing. Application October 28, 1932 SerialNo. 640,129

9 Claims.

The present invention relates to improvements in substitutedhalogen-phenols and particularly in halogen-phenols in which twohydrocarbon radicals are substituted in the ring.

In accordance with the present invention we have formed suchhalogen-phenols having two hydrocarbon radicals substituted in the ring,in which the sum of the carbon atoms in the two ring-substitutinghydrocarbon radicals is at least five, and in which one of thesubstituting radicalsmay be an alkyl, cycloalkyl, arylalkyl or otherhydrocarbon radical. We have found that such compounds are effectivebactericidal agents and are particularly effective with respect tomicro-organisms of the type of Staphylococcus aureas.

For simplicity in description of methods for the production of compoundsin accordance with our invention, we have referred hereinafter largelyto chloro-substituted phenols. It is to be understood, however, thatsimilar methods may be employed, using other halogens, such as bromineor iodine, as the substituents.

A methyl-butyl-halogen phenol may be prepared in the following manner: Ahalogenated cresol, such as p-chloro-m-cresol is mixed with ZnClz in theproportions of parts of the former and 52 parts of the latter, and themixture is heated to 80 C. Sec.-buty1 bromideis added very slowly untilthe equivalent proportion has been added, while maintaining the mixtureat 80 to 90 C., and the heating is continued for some time after thebutyl bromide has been added for completion of the reaction. The mixtureis extracted with a methyl alcoholic alkali solution and purified,suitably by repeated precipitation and extraction and the resultingcompound further purified by vacuum distillation. The resulting productis 3-methyl-6 sec. butyl-4-chlcrophenol. It distills at 125-127" C. at 3mm. hg. Its phenol coefficient with respect to B. tvphosus i550, andwith respect to Staph. aureus is 500.

In place of sec. butyl bromide other halogensubstituted hydrocarbons maybe employed in the reaction. Instead of the halogen-substitutedhydrocarbons, the alcohols may be employed in the reaction.

For example, a methyl-amyl-halogen phenol may be prepared as follows: 72parts of p-ch1orom-cresol is heated with a mixture of-44 parts of anamyl alcohol (e. g., diethyl carbinol) and 77 parts or concentratedHaSO4 at a temperature of about 90 C. for three hours, the sulfuricacidalcohol mixture having been added slowly over a period of one hourwith constant stirring. The

resulting compound is removed by extraction with methyl alcoholicalkali, and purified by repeated precipitation and re-extraction andfinally by vacuum distillation. The product distills at 132- 135 C. at 2mm. hg. Its phenol coefficient with respect to Staph. aureus is 620.

In a similar manner, by condensing p-chlorom-cresol with n-octyl alcoholin the presence of a condensing agent, such as 88% H2804, 6-sec.octyl-3-methyl-4-chlorophenol may be prepared. On purification it isfound to boil at 157-l59 C. at 2 mm. hg. It is an efl'ectivebactericide.

In the preceding example, sulfuric acid has been referred to as anexample of suitable condensing agents. It is readily apparent that othercondensing agents may be employed, such as anhydrous zinc chloride,ferric chloride, alumi-- num chloride and the like.

Compounds according to the present invention may be made in variousways. For example, by reacting on a suitable halogenated phenol havingone substituting hydrocarbon radical with an acyl chloride, thecorresponding ester may be formed. This, on treatment with a suitableagent, such as A1013, forms the corresponding ketone, and the ketone,after purification, may be reduced to form the second hydrocarbonsubstituting radical. The progress of the reaction may be indicated asfollows:

R -x-CaHJ-OH R -X-CsHa-O-COR=- R -XR'CO-CaH2-OH R -X'R'CH2-CsH2OHwherein R and It are hydrocarbon radicals and x represents a halogenatom.

Thus, using initially p-chloro-ortho-cresol and 9 butyryl chloride,there may be produced 2- methyl-4-chloro-B-butyl-phenol. Correspondingderivatives may be prepared by employing initially bromooriodo-monoalkyl phenols and by employing other acid chlorides; forexample, by using phenyl acetyl chloride, the correspondingS-methyl-B-phenyl ethyl-4-chlcrophenol may be formed. I

Instead of employing a halogenated phenol initially, a hydrocarbonsubstituted phenol may be used and the halogen subsequently introduced.-Thus, by employing initially a substituted phenol such as p-RJ-CsmOI-I,condensing it with a compound of the formula RBr or ROH, using suitablecondensing agents such as sulfuric acid, zinc chloride or aluminumchloride, and halogenating the product, a compound of the formula maybe' formed, R and R. indicating hydrocarbon radicals and X a halogen.

Other methods oi. forming products in accordance with the presentinvention may be employed. For example, by reacting on para-ethylphenolwith propionyl chloride, ethyl-phenylpropionate is produced. It isseparated, purified and treated with AlCIs, a rearrangement taking placewith the formation of 5-ethyl-2-hydroxy propiophenone. On reduction ofthis compound 4-ethyl-2-propyl-phenol is formed and on treatment of thelatter with sulphuryl chloride, 4- ethyl-2-propyl-fi-chloro-phenol isproduced. It dlstills at 116 C. at 3 mm. hg. and has a high bactericidalvalue. By using other halogenating agents, other halogen groups may beintroduced.

In compounds of the present invention, it is our belief that the totalmolecular weight of the substituting hydrocarbon radicals is ofimportance in securing products of high bactericidal potency and we havefound that compounds in which the sum of the carbon atoms in the twosubstituting hydrocarbon radicals is at least 5 are highly effectivebactericides, and particularly with respect to organisms of the type ofStaphylococcus aureus.

We claim:

1. A mono-halogenated phenol having two substituting hydrocarbonradicals in the ring, the sum of the carbon atoms of the twosubstituting radicals being at least 5.

2. A dialkyl mono-halogenated phenol in which the sum of the carbon atomof the two alkyl groups is at least 5.

3. A dialkyl chloro-phenol in which the sum of the carbon atoms of thetwo alkyl groups is at least 5.

. An alkyl-arylalkyl halogen phenol. An alkyl-phenoyl ethylchlorophenol. 3-methyl-6-(diethyl methyl) -4-chlorophe- A3-methyl-6-alkyl-4-halogen-phenol.

. 4-ethyl-2-propyl-6-chlorophenol.

. 3-methyl-6-phenylethyl-4-chl0rophenol.

EMIL KLARMANN. LOUIS W. GATES.

i3 eacoq mona CERTIFICATE OF CORRECTION.

Patent No. "1,938,911.

December 12, 1933.

EMIL KLARMANN, ET AL.

It is hereby certified that error appears in the printed specificationof the above numbered patent requiring correction as follows: Page 1,lines 40, 60 and 67, and page 2, line 12, respectively, for "lig" readHg; page 2, line 90, claim 5. for alkyl-phencyl" read alkyl-phenyl; andthat the said Letters Patent should be read with these correctionstherein that the same may conform to the record of the case in thePatent Office.

Signed'and sealed this 16th day of. January, A. D. 1934.

(Seal) F. M. Hopkins Acting Commissioner of Patents.

